This project is designed to determine the cause of increased orotic acid excretion in animals consuming diets that are marginal or deficient in arginine or other urea cycle intermediates. The present studies will determine the influence of dietary arginine deficiency upon the activities of enzymes in the pyrimidine biosynthetic pathway. Additional studies will examine the flux of intermediates through orotic acid biosynthesis and the subsequent incorporation into RNA and DNA. Studies will examine the relationship of increased orotic aciduria in the arginine deficient rat to an inability of the urea cycle to detoxify excess nitrogen.